The Evolutionary Advantage in Mammals of the Complementary Monoallelic Expression Mechanism of Genomic Imprinting and Its Emergence From a Defense Against the Insertion Into the Host Genome.

Tomoko Kaneko-Ishino,Fumitoshi Ishino

doi:10.3389/fgene.2022.832983

Tomoko Kaneko-Ishino, Fumitoshi Ishino

Open Access

https://doi.org/10.3389/fgene.2022.832983

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Abstract

In viviparous mammals, genomic imprinting regulates parent-of-origin-specific monoallelic expression of paternally and maternally expressed imprinted genes (PEGs and MEGs) in a region-specific manner. It plays an essential role in mammalian development: aberrant imprinting regulation causes a variety of developmental defects, including fetal, neonatal, and postnatal lethality as well as growth abnormalities. Mechanistically, PEGs and MEGs are reciprocally regulated by DNA methylation of germ-line differentially methylated regions (gDMRs), thereby exhibiting eliciting complementary expression from parental genomes. The fact that most gDMR sequences are derived from insertion events provides strong support for the claim that genomic imprinting emerged as a host defense mechanism against the insertion in the genome. Recent studies on the molecular mechanisms concerning how the DNA methylation marks on the gDMRs are established in gametes and maintained in the pre- and postimplantation periods have further revealed the close relationship between genomic imprinting and invading DNA, such as retroviruses and LTR retrotransposons. In the presence of gDMRs, the monoallelic expression of PEGs and MEGs confers an apparent advantage by the functional compensation that takes place between the two parental genomes. Thus, it is likely that genomic imprinting is a consequence of an evolutionary trade-off for improved survival. In addition, novel genes were introduced into the mammalian genome via this same surprising and complex process as imprinted genes, such as the genes acquired from retroviruses as well as those that were duplicated by retropositioning. Importantly, these genes play essential/important roles in the current eutherian developmental system, such as that in the placenta and/or brain. Thus, genomic imprinting has played a critically important role in the evolutionary emergence of mammals, not only by providing a means to escape from the adverse effects of invading DNA with sequences corresponding to the gDMRs, but also by the acquisition of novel functions in development, growth and behavior via the mechanism of complementary monoallelic expression.

Highlights

Genomic imprinting is widely distributed in the viviparous mammals, the therians, comprising marsupials and eutherians (Reik and Walter 2001; Renfree et al, 2009; Barlow and Bartolomei 2014), yet it is an unusual biological mechanism in that it seems to runs counter to two main pillars of modern biology: it is an apparent exception to the rule of Mendelian genetics that presupposes biallelic expression from two parental alleles, and it is inconsistent with the Darwinian theory of evolution at first glance due to the apparent disadvantage (Mann and Lovell-Badge, 1984; McGrath and Solter 1984; Surani et al, 1984; Cattanach and Kirk 1985) of the monoallelic expression of certain essential/important genes in development
It is difficult to prove these hypotheses by experiment, these features are surely advantageous for viviparous mammals and seem to have been acquired from the beginning via genomic imprinting, because the first two imprinted regions established in a common therian ancestor were the PEG10 and H19/Insulin-like growth factor 2 (IGF2) regions (Figure 3), that exert potent effects on placental formation and growth, respectively
Accumulating evidence has painted a picture of a close relationship between genomic imprinting and invading DNA: 1) the insertion of DNA sequences corresponding to the germ-line differentially methylated regions (gDMRs) (Figure 3), 2) retroviral long terminal repeats (LTRs) are used as promoters of oocytespecific transcripts for DNA methylation on the gDMRs (Figure 4B), 3) the antiviral Kru€ppel-associated box (KRAB)-zinc finger proteins (ZFPs) system protects the gDMRs from global DNA demethylation (Figure 4C), providing strong support for the host defense hypothesis

Summary

Introduction

Genomic imprinting is widely distributed in the viviparous mammals, the therians, comprising marsupials and eutherians (Reik and Walter 2001; Renfree et al, 2009; Barlow and Bartolomei 2014), yet it is an unusual biological mechanism in that it seems to runs counter to two main pillars of modern biology: it is an apparent exception to the rule of Mendelian genetics that presupposes biallelic expression from two parental alleles, and it is inconsistent with the Darwinian theory of evolution at first glance due to the apparent disadvantage (Mann and Lovell-Badge, 1984; McGrath and Solter 1984; Surani et al, 1984; Cattanach and Kirk 1985) of the monoallelic expression of certain essential/important genes in development. These results indicate that DNA methylation on the gDMRs is necessary to induce the repressed genes in the default state, indicating the strict requirement of having both paternal and maternal epigenotypes, leading to the complementary expression of PEGs and MEGs (Kaneko-Ishino et al, 2003; Kaneko-Ishino et al, 2006).

Results

Conclusion